Entä miten nämä toimivat aivossa?
Aivossa tarvitaan jatkuvaa rasva-aine ja kolesterolisynteesiä, koska aivo on rasvamoduli, koostunut hyvin monimutkaisista j monipuolisista lipidiaineista. Lisäksi neuronit tarvitsevat AcetylCoaa muodostamaan hermonvälittäjäainetta asetylkoliinia kolinergisessä järjestelmässä. Se toimii eräänlaisena clearing-tekijänä hermoissa ja varsinkin tahdonalaisessa ajattelussa ja toiminnassa se on tärkeä. hermorata. Löytyykö jotain konkreettista karttaa sitraatista, kelch-proteiinifunktiosta, ja yhteydestä muihin elementaarisiin etikkahapon ja sitruunahapon tasoa kuvaaviin kaavoihin?
Cullin3–KLHL25 ubiquitin ligase targetsACLY for degradation to inhibit lipidsynthesis and tumor progression
Cen Zhang,1,4Juan Liu,1,4Grace Huang,2Yuhan Zhao,1Xuetian Yue,1Hao Wu,1Jun Li,1Junlan Zhu,2Zhiyuan Shen,1Bruce G. Haffty,1Wenwei Hu,1and Zhaohui Feng1,31Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, The State Universityof New Jersey, New Brunswick, New Jersey 08903, USA;2Nelson Institute of Environmental Medicine, New York UniversitySchool of Medicine, New York University, Tuxedo, New Jersey 10987, USA;3Department of Pharmacology, Rutgers University,The State University of New Jersey, Piscataway, New Jersey 08854, USA
Increased lipid synthesis is a key characteristic of many cancers that is critical for cancer progression. ATP-citratelyase (ACLY), a key enzyme for lipid synthesis, is frequently overexpressed or activated in cancer to promote lipidsynthesis and tumor progression. Cullin3 (CUL3), a core protein for the CUL3–RING ubiquitin ligase complex, has been reported to be a tumor suppressor and frequently down-regulated in lung cancer. Here, we found that CUL3interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate anddegrade ACLY in cells. Through negative regulation of ACLY, CUL3 inhibits lipid synthesis, cell proliferation,and xenograft tumor growth of lung cancer cells. Furthermore, ACLY inhibitor SB-204990 greatly abolishes thepromoting effect of CUL3 down-regulation on lipid synthesis, cell proliferation, and tumor growth. Importantly, lowCUL3 expression is associated with high ACLY expression and poor prognosis in human lung cancer. In summary,our results identify CUL3–KLHL25 ubiquitin ligase as a novel negative regulator for ACLY and lipid synthesis anddemonstrate that decreased CUL3 expression is an important mechanism for increased ACLY expression and lipidsynthesis in lung cancer. These results also reveal that negative regulation of ACLY and lipid synthesis is a novel andcritical mechanism for CUL3 in tumor suppression.[Keywords: CUL3; ACLY; KLHL25; ubiquitination; lipid synthesis; tumor
https://www.ncbi.nlm.nih.gov/pubmed/28161643
SIRT3 have been
found to be neuroprotective in many neurological diseases, but its
detail mechanism is only partially understood. In this study, MPP+
was used to treat SH-SY5Y cells as the cellular model of PD to test the
role of SIRT3 and the mechanism may be involved in. We focused on the
changes and relationship between SIRT3 and the key mitochondrial enzymes
citrate synthase (CS) and isocitrate dehydrogenase 2 (IDH2). We found MPP+
decreased SIRT3 expression. And our results showed that the enzymatic
activities of CS and IDH2 were significantly reduced in MPP+
treatment cells, while protein acetylation of CS and IDH2 increased.
However overexpressed-SIRT3 partially reversed at least, the decline of
CS activity and the increase of CS protein acetylation. IDH2 did not
showed the same changes. The study suggested that SIRT3 deacetylated and
activated CS activity. Hence, we conclude that SIRT3 exhibits
neuroprotection via deacetylating and increasing mitochondrial enzyme
activities.
Copyright © 2017 Elsevier Inc. All rights reserved.
Deacetylation; Enzyme activity; Mitochondria; Neuroprotection; Parkinson disease; SIRT3
https://i.pinimg.com/originals/b0/bd/44/b0bd4471753eb332a4d601c7e065ee6e.jpg
https://i.pinimg.com/originals/b0/bd/44/b0bd4471753eb332a4d601c7e065ee6e.jpg
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